Ester derivatives of the Formula I
    wherein R1 is —CN, —OP, alkyl, aryl or heteroaryl;    wherein P represents any suitable protecting group; and R2 is alkyl or aryl;are valuable chiral synthons for synthesizing compounds which are known anti-hyptercholesterolemic agents having an inhibitory effect on HMG-CoA reductase (See U.S. Pat. Nos. 5,003,080, 5,169,857, 5,354,772; PCT Application WO 01 85702; European Patent Application EP 0304063).
The most common approach for achieving stereoselective synthesis of compounds of Formula I is the reduction of Formula II
    wherein R1 is —CN, —OP, alkyl, aryl or heteroaryl; wherein P represents any suitable protecting group; and R2 is alkyl or aryl;    using special borane reagents (See U.S. Pat. Nos. 5,273,995, 5,470,981, 5,489,691). However, reagents such as methoxydiethylborane are hazardous and expensive.
U.S. Pat. No. 6,001,615 describes an enzymatic synthetic route. This process, however, is not industrially scalable and involves large volumes.
U.S. Pat. No. 5,399,722 describes a process starting from commercially available ethyl-ω-chloroacetoacetate or its benzyloxy derivative. Disadvantages of this process are that a stereoselective reduction using a ruthenium-BINAP catalyst is employed and the desired compound of Formula I is obtained in six steps.
U.S. Pat. No. 5,481,009 describes a process starting from 4-phenyl-3-butenoic acid and achieves the desired compound in about 5 steps. The process uses hazardous steps (e.g. ozonolysis) to obtain the desired product.
Exemplary synthetic approaches for the preparation of statins using compounds of Formula I are depicted in Schemes 1-6.
The present invention has several advantages over known methods. The process of the present invention is safe and non-hazardous, cost-effective, industrially scalable, requires few steps, and is commercially viable.